INFECTIOUS ETIOLOGY

OVERVIEW

The commonest etiology for epilepsy worldwide is infectious,
especially in developing countries. Infections in the central nervous
system can cause both acute symptomatic seizures (which occur closely
related to the timing of the initial infection) and epilepsy.
Infectious etiologies include tuberculosis, HIV, cerebral malaria,
neurocysticercosis, subacute sclerosing panencephalitis, cerebral
toxoplasmosis. These infections sometimes have a structural correlate,
however the primary cause of the epilepsy is conceptualized as the
infectious process. An infectious etiology may have specific treatment
implications. There are also public health implications as prevention
of such infections may reduce the burden of epilepsy, particularly in
developing countries.

The commonest etiologies for bacterial meningitis are
meningococus, pneumococcus and haemophilus influenza B. Acute seizures
may occur related to fever or to complications such as subdural
collections, cerebritis or cerebral infarction. Immunization programs
may reduce the incidence of specific bacterial meningitides.

Plasmodium falciparum in sub-Saharan Africa can cause neurologic
complications in half of affected individuals. This infection is the
most important cause of epileptic seizures in these regions. Cerebral
malaria with related coma may be fatal, especially in children.
Plasmodium vivax in Asia causes similar neurological complications and
epilepsy.

Toxoplasmosis, found worldwide, is caused by Toxoplasma gondii.
Immunocompetent persons with primary infection are usually
asymptomatic, but latent infection can occur. In immunosuppressed
patients, especially those with HIV, reactivation can cause disease
(usually when CD4 lymphocyte count falls below 100 cells/mm3). Most
patients with cerebral toxoplasmosis have multiple, ring-enhancing,
brain lesions often associated with edema and with predilection for
involvement of the basal ganglia.

CMV is the commonest fetal viral infection. Fetal CNS infection
after 20 weeks gestation can cause malformations of cortical
development (including polymycrogyria
and schizencephaly),
and intracranial calcification in the developing brain.
Direct perinatal CNS CMV infection can also occur, with clinical
signs manifesting after an incubation period of 2-6 weeks. Overall,
90% of affected infants are asymptomatic at birth, resulting in
challenges in early correct diagnosis of CMV neuroinfection. Some of
these infants may only present with sensorineural hearing loss at a
later date. However, 10% of infants may have early symptoms which
may include microcephaly, anaemia, thrombocytopenia, hepatitis,
chorioretinitis, neurological impairment and sensorineural hearing
impairment. Diagnosis is by detection of CMV DNA in CSF. CMV DNA may
also be detected in in urine. Seizures may have onset in the first
month of life, in the first year or rarely later. Treatment with
gancyclovir may ameliorate the clinical course.

Seizures can result from primary cerebral HIV infection,
especially in children. In adults, most seizures are cause by related
opportunistic central nervous system infections such as toxoplasmosis,
cryptococcal meningitis and tuberculomas; or due to secondary
neoplastic lesions.

Neurocysticercosis is caused by ingestion of food contaminated
with Taenia solium eggs. Eggs hatch in the intestine, larvae migrate
to the central nervous system and then form cysts. Cysts have four
phases: 1) vesicular (asymptomatic); 2) colloidal (degeneration and
inflammation); 3) granular nodular; and 4) calcification. Although
seizures are most often associated with cyst degeneration, they can
occur at any stage. Although neurocysticercosis is more prevalent in
developing countries (Latin-America, India and Africa), individuals in
developed countries may be affected, if they have had foreign travel
to endemic areas.

The diagnosis of neurocysticercosis is complex; no diagnostic
test identifies all cases. The diagnosis depends on supportive
clinical history (including exposure history), laboratory results and
imaging findings. In most patients, neuroimaging findings are not
pathognomonic. If an eccentric scolex is seen within the cyst,
neurocystericosis may be diagnosed confidently. During the
degeneration of the cyst, contrast-enhancing lesions with surrounding
edema may be observed on imaging. Enzyme-linked immunotransfer
blotting is the most accurate serologic test. A negative serologic
result does not exclude neurocysticercosis. The sensitivity of this
test is higher early in the course of infection (when individuals are
often asymptomatic) and lower late in the disease course (when
individuals are symptomatic, and lesions calcified). The sensitivity
in the presence of multiple intracranial cysts is higher (90-100%) but
lower (20-30%) when inflammation is absent or in the presence of a
single cyst.

Seizures can occur in meningo-tuberculosis due to cerebral
vasculitis and infarction, especially in young children and in people
co-infected with HIV. Seizures with focal features may also occur as a
consequence of tuberculomas, identified as ring-enhancing lesions on
neuroimaging.

Encephalitis is a recognized complication of infections with a
number of viruses. Herpes simplex virus type 1 is the most common
viral cause. Affected individuals present with acute encephalopathy
and seizures, epilepsy develops in around 50% of cases. Other less
common etiologies for viral encephalitis include human herpes virus 6
(associated with acute limbic encephalitis and febrile status
epilepticus), influenza B, varicella, measles, mumps and rubella
viruses. In certain countries or regions there is a predominance of
specific viral etiologies for encephalitis, examples include Japanese
and enterovirus 71 in Asia, West Nile virus in the USA, arbovirus in
Europe and Dengue virus in some African and Latin-American countries.

Sub-acute sclerosing panencephalitis is a rare progressive
chronic encephalitis, seen predominantly in children and young adults
as a consequence of chronic measles infection (typically with the
initial infection occurring before the age of 2 years). Affected
individuals show progressive cognitive deterioration, seizures
(myoclonus), ataxia, photosensitivity, and a characteristic EEG
(periodic discharges).